GZMB
protein-codinggranzyme B, the group of Granule associated serine proteases of immune defence
Gene summary
This gene encodes a member of the granzyme subfamily of proteins, part of the peptidase S1 family of serine proteases. The encoded preproprotein is secreted by natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) and proteolytically processed to generate the active protease, which induces target cell apoptosis. This protein also processes cytokines and degrades extracellular matrix proteins, and these roles are implicated in chronic inflammation and wound healing. Expression of this gene may be elevated in human patients with cardiac fibrosis. [provided by RefSeq, Sep 2016]
- CTLA1
- CSPB
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GZMB variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004131.6. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 2 | 1 | 4 | ||
| missense | 41 | 2 | 43 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 42 | 4 | 1 | 47 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004122.2 | 5 | MANE Select | |
| Ensembl | ENSP00000216341.4 | 5 | MANE Select | |
| RefSeq | NP_001332940.1 | 5 | Standard | |
| Ensembl | ENSP00000371980.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Type I diabetes mellitus - Homo sapiens (human)
- Allograft rejection - Homo sapiens (human)
- Graft-versus-host disease - Homo sapiens (human)
- Autoimmune thyroid disease - Homo sapiens (human)
- Natural killer cell mediated cytotoxicity - Homo sapiens (human)
Biological Process
- proteolysis
- apoptotic process
- granzyme-mediated apoptotic signaling pathway
- cytolysis
- natural killer cell mediated cytotoxicity
Molecular Function
- serine-type endopeptidase activity
- protein binding
- serine-type peptidase activity
Cellular Component
- immunological synapse
- nucleus
- cytoplasm
- mitochondrion
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000216341
- Coding exons
- 5
- Length
- 3314
- Individuals with no LoFs
- 125704
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 43
- Defined
- 125747
- p
- 0.000171
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.306 | 153 | 143 | 1.07 | 0.00000779 | 1605 |
| Missense (PolyPhen) | 49 | 44.552 | 1.0998 | 503 | ||
| Synonymous | -1.24 | 67 | 55.3 | 1.21 | 0.00000324 | 482 |
| Loss of Function | -1.71 | 17 | 10.9 | 1.56 | 5.42e-7 | 113 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00018 | 0.00017 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00020 | 0.00019 | rare |
| South Asian | 0.00023 | 0.00023 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: This enzyme is necessary for target cell lysis in cell- mediated immune responses. It cleaves after Asp. Seems to be linked to an activation cascade of caspases (aspartate-specific cysteine proteases) responsible for apoptosis execution. Cleaves caspase-3, -7, -9 and 10 to give rise to active enzymes mediating apoptosis.;
Recessive Scores
- pRec
- 0.526
Intolerance Scores
- LoFtool
- 0.415
- RVIS EVS
- 0.31
- RVIS percentile EVS
- 72.23
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.501
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |